NEW ORLEANS – There should be no hesitation to use rituximab or cyclophosphamide in anti–N-methyl-d-aspartate receptor encephalitis patients who do not respond to steroids, immunoglobulins, or plasma exchange within the first 4 weeks, according to neurologist Maarten Titulaer, the lead investigator on a 467-patient study of the disease.
"Treat aggressively. The quicker you treat, the better the outcome. If first-line therapy fails, progress to second-line treatment," said Dr. Titulaer, a visiting research fellow at the University of Pennsylvania, Philadelphia.
Rituximab (Rituxan) and cyclophosphamide made relapse less likely. "The chance is only 5% that [patients] will relapse in the first 2 years" if they received either drug. "It was 20% in patients treated only with, for example, steroids or [intravenous immunoglobulin]," he said at the annual meeting of the American Academy of Neurology.
Dr. Titulaer’s team tracked 2-year outcomes in the patients. Just over half responded to first-line treatment within 4 weeks. Of those, 98% were back home and independent in daily activities within 2 years; 90% had returned to school or work.
Just under half, however, did not respond to first-line agents; just over half of those went on to either rituximab or cyclophosphamide. Of those, 55% recovered fully within 2 years, 76% were back home and independent in daily activities, and about 20% had died or were in a vegetative state.
Of those who did not get rituximab or cyclophosphamide after failing first-line treatments but who instead got another round of those treatments or no further treatment, 37% were fully recovered at 2 years; 55% were back home and independent in daily activities; and 33% had died or were in a vegetative state. The differences in response between the groups after they failed first-line therapies were statistically significant.
In a group of approximately 25 patients who were not treated at all because the diagnosis was missed (or for some other reason), 38% were dead or in a vegetative state after 2 years.
First identified in 2007, N-methyl-d-aspartate (NMDA) receptor encephalitis predominately attacks young women and is associated with ovarian teratomas. The disease is thought to be caused by an autoantibody attack on subunits of brain NMDA glutamate receptors, which are believed to control synaptic plasticity and memory function (N. Engl. J. Med. 2009;361:302-3).
In all, 81% of the cases were female; their median age was 19 years (range, 1-85 years). In patients younger than 12 years and older than 45 years of age, incidence split more evenly between sexes. A tumor occurred in 39% of patients, and almost all were teratomas. An ovarian teratoma occurred in 54% of females older than 12 years, compared with only 4% of girls younger than 12. Patients with tumors had slightly more severe disease.
Immunotherapy plus tumor removal, when appropriate, resulted in full recovery or substantial improvement in about two-thirds of patients by 8 months, and in 77% at 2 years. Relapses occurred in 14% of patients, about three-quarters of them without teratomas.
As currently understood, the disease has protean manifestations, including cognitive problems, psychiatric issues, seizures, dyskinesias, decreased consciousness, behavioral changes, autonomic instability, hypoventilation, movement disorders, and memory and speech disorders.
Almost all of the patients in the study presented with three or more of those symptoms. Adults tended to present with behavioral changes and memory problems; children tended to present with seizures, movement disorders, and – less commonly – abnormal behavior. Within the first month, memory problems and hypoventilation were more common in adults; movement disorders and ataxia were more frequent in children.
Dr. Titulaer said that he had no disclosures.